diff --git a/Library/Homebrew/cleanup.rb b/Library/Homebrew/cleanup.rb
index d31a51fca1..e381088a1d 100644
--- a/Library/Homebrew/cleanup.rb
+++ b/Library/Homebrew/cleanup.rb
@@ -160,7 +160,7 @@ module Homebrew
       cleanup = Cleanup.new(dry_run: dry_run)
       if cleanup.periodic_clean_due?
         cleanup.periodic_clean!
-      elsif f.latest_version_installed? && !cleanup.skip_clean_formula?(f)
+      elsif f.latest_version_installed? && !Cleanup.skip_clean_formula?(f)
         ohai "Running `brew cleanup #{f}`..."
         puts_no_install_cleanup_disable_message_if_not_already!
         cleanup.cleanup_formula(f)
@@ -177,7 +177,7 @@ module Homebrew
       @puts_no_install_cleanup_disable_message_if_not_already = true
     end
 
-    def skip_clean_formula?(f)
+    def self.skip_clean_formula?(f)
       return false if Homebrew::EnvConfig.no_cleanup_formulae.blank?
 
       skip_clean_formulae = Homebrew::EnvConfig.no_cleanup_formulae.split(",")
@@ -215,7 +215,7 @@ module Homebrew
       if args.empty?
         Formula.installed
                .sort_by(&:name)
-               .reject { |f| skip_clean_formula?(f) }
+               .reject { |f| Cleanup.skip_clean_formula?(f) }
                .each do |formula|
           cleanup_formula(formula, quiet: quiet, ds_store: false, cache_db: false)
         end
@@ -256,7 +256,7 @@ module Homebrew
             nil
           end
 
-          if formula && skip_clean_formula?(formula)
+          if formula && Cleanup.skip_clean_formula?(formula)
             onoe "Refusing to clean #{formula} because it is listed in " \
                  "#{Tty.bold}HOMEBREW_NO_CLEANUP_FORMULAE#{Tty.reset}!"
           elsif formula
@@ -264,8 +264,6 @@ module Homebrew
           end
           cleanup_cask(cask) if cask
         end
-
-        Cleanup.autoremove(dry_run: dry_run?) if Homebrew::EnvConfig.autoremove?
       end
     end
 
@@ -526,7 +524,17 @@ module Homebrew
     end
 
     def self.autoremove(dry_run: false)
-      removable_formulae = Formula.unused_formulae_with_no_dependents
+      require "cask/caskroom"
+
+      # If this runs after install, uninstall, reinstall or upgrade,
+      # the cache of installed formulae may no longer be valid.
+      Formula.clear_cache unless dry_run
+
+      # Remove formulae listed in HOMEBREW_NO_CLEANUP_FORMULAE.
+      formulae = Formula.installed.reject(&method(:skip_clean_formula?))
+      casks = Cask::Caskroom.casks
+
+      removable_formulae = Formula.unused_formulae_with_no_dependents(formulae, casks)
 
       return if removable_formulae.blank?
 
@@ -541,6 +549,9 @@ module Homebrew
 
       kegs_by_rack = removable_formulae.map(&:any_installed_keg).group_by(&:rack)
       Uninstall.uninstall_kegs(kegs_by_rack)
+
+      # The installed formula cache will be invalid after uninstalling.
+      Formula.clear_cache
     end
   end
 end
diff --git a/Library/Homebrew/cmd/leaves.rb b/Library/Homebrew/cmd/leaves.rb
index f14bed7dfc..ec134de4a1 100644
--- a/Library/Homebrew/cmd/leaves.rb
+++ b/Library/Homebrew/cmd/leaves.rb
@@ -37,7 +37,7 @@ module Homebrew
   def leaves
     args = leaves_args.parse
 
-    leaves_list = Formula.installed_formulae_with_no_formula_dependents
+    leaves_list = Formula.formulae_with_no_formula_dependents(Formula.installed)
 
     leaves_list.select!(&method(:installed_on_request?)) if args.installed_on_request?
     leaves_list.select!(&method(:installed_as_dependency?)) if args.installed_as_dependency?
diff --git a/Library/Homebrew/formula.rb b/Library/Homebrew/formula.rb
index 5caa3876fd..4db86ebed3 100644
--- a/Library/Homebrew/formula.rb
+++ b/Library/Homebrew/formula.rb
@@ -1708,29 +1708,26 @@ class Formula
 
   # An array of all installed {Formula} with {Cask} dependents.
   # @private
-  def self.installed_formulae_with_cask_dependents
-    require "cask/caskroom"
-
-    Cask::Caskroom.casks
-                  .flat_map { |cask| cask.depends_on[:formula] }
-                  .compact
-                  .map { |f| Formula[f] }
-                  .flat_map { |f| [f, *f.runtime_formula_dependencies].compact }
+  def self.formulae_with_cask_dependents(casks)
+    casks.flat_map { |cask| cask.depends_on[:formula] }
+         .compact
+         .map { |f| Formula[f] }
+         .flat_map { |f| [f, *f.runtime_formula_dependencies].compact }
   end
 
   # An array of all installed {Formula} without {Formula} dependents
   # @private
-  def self.installed_formulae_with_no_formula_dependents(formulae = installed)
+  def self.formulae_with_no_formula_dependents(formulae)
     return [] if formulae.blank?
 
     formulae - formulae.flat_map(&:runtime_formula_dependencies)
   end
 
-  # Recursive function that returns an array of installed {Formula} without
+  # Recursive function that returns an array of {Formula} without
   # {Formula} dependents that weren't installed on request.
   # @private
   def self.unused_formulae_with_no_formula_dependents(formulae)
-    unused_formulae = installed_formulae_with_no_formula_dependents(formulae).reject do |f|
+    unused_formulae = formulae_with_no_formula_dependents(formulae).reject do |f|
       Tab.for_keg(f.any_installed_keg).installed_on_request
     end
 
@@ -1741,12 +1738,12 @@ class Formula
     unused_formulae
   end
 
-  # An array of installed {Formula} without {Formula} or {Cask}
+  # An array of {Formula} without {Formula} or {Cask}
   # dependents that weren't installed on request.
   # @private
-  def self.unused_formulae_with_no_dependents
-    unused_formulae = unused_formulae_with_no_formula_dependents(installed)
-    unused_formulae - installed_formulae_with_cask_dependents
+  def self.unused_formulae_with_no_dependents(formulae, casks)
+    unused_formulae = unused_formulae_with_no_formula_dependents(formulae)
+    unused_formulae - formulae_with_cask_dependents(casks)
   end
 
   def self.installed_with_alias_path(alias_path)
diff --git a/Library/Homebrew/test/formula_spec.rb b/Library/Homebrew/test/formula_spec.rb
index e8f3fa81d6..1ed7890557 100644
--- a/Library/Homebrew/test/formula_spec.rb
+++ b/Library/Homebrew/test/formula_spec.rb
@@ -446,40 +446,133 @@ describe Formula do
     end
   end
 
-  describe "::installed_formulae_with_no_formula_dependents" do
-    let(:formula_is_dep) do
-      formula "foo" do
-        url "foo-1.1"
+  shared_context "with formulae for dependency testing" do
+    let(:formula_with_deps) do
+      formula "zero" do
+        url "zero-1.0"
       end
     end
 
-    let(:formula_with_deps) do
-      formula "bar" do
-        url "bar-1.0"
+    let(:formula_is_dep1) do
+      formula "one" do
+        url "one-1.1"
+      end
+    end
+
+    let(:formula_is_dep2) do
+      formula "two" do
+        url "two-1.1"
       end
     end
 
     let(:formulae) do
       [
         formula_with_deps,
-        formula_is_dep,
+        formula_is_dep1,
+        formula_is_dep2,
       ]
     end
 
     before do
-      allow(formula_with_deps).to receive(:runtime_formula_dependencies).and_return([formula_is_dep])
+      allow(formula_with_deps).to receive(:runtime_formula_dependencies).and_return([formula_is_dep1,
+                                                                                     formula_is_dep2])
+      allow(formula_is_dep1).to receive(:runtime_formula_dependencies).and_return([formula_is_dep2])
     end
+  end
 
-    specify "without formulae parameter" do
-      allow(described_class).to receive(:installed).and_return(formulae)
+  describe "::formulae_with_no_formula_dependents" do
+    include_context "with formulae for dependency testing"
 
-      expect(described_class.installed_formulae_with_no_formula_dependents)
+    it "filters out dependencies" do
+      expect(described_class.formulae_with_no_formula_dependents(formulae))
           .to eq([formula_with_deps])
     end
+  end
 
-    specify "with formulae parameter" do
-      expect(described_class.installed_formulae_with_no_formula_dependents(formulae))
-          .to eq([formula_with_deps])
+  describe "::unused_formulae_with_no_formula_dependents" do
+    include_context "with formulae for dependency testing"
+
+    let(:tab_from_keg) { double }
+
+    before do
+      allow(Tab).to receive(:for_keg).and_return(tab_from_keg)
+    end
+
+    specify "installed on request" do
+      allow(tab_from_keg).to receive(:installed_on_request).and_return(true)
+      expect(described_class.unused_formulae_with_no_formula_dependents(formulae))
+          .to eq([])
+    end
+
+    specify "not installed on request" do
+      allow(tab_from_keg).to receive(:installed_on_request).and_return(false)
+      expect(described_class.unused_formulae_with_no_formula_dependents(formulae))
+          .to eq(formulae)
+    end
+  end
+
+  shared_context "with formulae and casks for dependency testing" do
+    include_context "with formulae for dependency testing"
+
+    require "cask/cask_loader"
+
+    let(:cask_one_dep) do
+      Cask::CaskLoader.load(+<<-RUBY)
+        cask "red" do
+          depends_on formula: "two"
+        end
+      RUBY
+    end
+
+    let(:cask_multiple_deps) do
+      Cask::CaskLoader.load(+<<-RUBY)
+        cask "blue" do
+          depends_on formula: "zero"
+        end
+      RUBY
+    end
+
+    let(:cask_no_deps1) do
+      Cask::CaskLoader.load(+<<-RUBY)
+        cask "green" do
+        end
+      RUBY
+    end
+
+    let(:cask_no_deps2) do
+      Cask::CaskLoader.load(+<<-RUBY)
+        cask "purple" do
+        end
+      RUBY
+    end
+
+    let(:casks_no_deps) { [cask_no_deps1, cask_no_deps2] }
+    let(:casks_one_dep) { [cask_no_deps1, cask_no_deps2, cask_one_dep] }
+    let(:casks_multiple_deps) { [cask_no_deps1, cask_no_deps2, cask_multiple_deps] }
+
+    before do
+      allow(described_class).to receive("[]").with("zero").and_return(formula_with_deps)
+      allow(described_class).to receive("[]").with("one").and_return(formula_is_dep1)
+      allow(described_class).to receive("[]").with("two").and_return(formula_is_dep2)
+    end
+  end
+
+  describe "::formulae_with_cask_dependents" do
+    include_context "with formulae and casks for dependency testing"
+
+    specify "no dependents" do
+      expect(described_class.formulae_with_cask_dependents(casks_no_deps))
+        .to eq([])
+    end
+
+    specify "one dependent" do
+      expect(described_class.formulae_with_cask_dependents(casks_one_dep))
+        .to eq([formula_is_dep2])
+    end
+
+    specify "multiple dependents" do
+      expect(described_class.formulae_with_cask_dependents(casks_multiple_deps))
+        .to eq(formulae)
     end
   end