diff --git a/Library/Homebrew/cleaner.rb b/Library/Homebrew/cleaner.rb
index 5df0e39b15865..8636ea7a0b4b3 100644
--- a/Library/Homebrew/cleaner.rb
+++ b/Library/Homebrew/cleaner.rb
@@ -59,6 +59,7 @@ def clean
       observe_file_removal info_dir_file
     end
 
+    rewrite_pkgconfig
     rewrite_shebangs
     clean_python_metadata
 
@@ -153,6 +154,48 @@ def clean_dir(directory)
     end
   end
 
+  sig { void }
+  def rewrite_pkgconfig
+    basepath = @formula.prefix.realpath
+    pc_files = %w[lib share].flat_map do |subdir|
+      pc_dir = basepath/subdir/"pkgconfig"
+      next [] if !pc_dir.exist? || @formula.skip_clean?(basepath/subdir) || @formula.skip_clean?(pc_dir)
+
+      pc_dir.glob("*.pc").reject { |pc_file| @formula.skip_clean?(pc_file) }
+    end
+    return if pc_files.empty?
+
+    # TODO: Add support for `brew unlink`-ed formulae and check on recursive dependencies
+    deps_pc_files = @formula.deps
+                            .filter_map { |dep| dep.to_formula if !dep.build? && !dep.test? }
+                            .select(&:keg_only?)
+                            .flat_map { |f| f.opt_prefix.glob("{lib,share}/pkgconfig/*.pc") }
+                            .to_h { |pc_file| [pc_file.basename(".pc").to_s.downcase, pc_file.to_s] }
+    deps_pc_modules_pattern = deps_pc_files.keys.map { |mod| Regexp.escape(mod) }.join("|")
+
+    pc_files.each do |pc_file|
+      modified_lines = pc_file.each_line.map do |line|
+        rewrote_prefix = line.gsub!(@formula.prefix.realpath.to_s, @formula.opt_prefix.to_s).present?
+        next [line, rewrote_prefix] if deps_pc_files.empty? || !line.start_with?(/Requires(?:\.private)?:/)
+
+        # pkgconf's pc.5 man page defines dependency list ABNF syntax as:
+        #
+        # > package-list = *WSP *( package-spec *( package-sep ) )
+        # > package-sep  = WSP / ","
+        # > package-spec = package-key [ ver-op package-version ]
+        # > ver-op       = "<" / "<=" / "=" / "!=" / ">=" / ">"
+        #
+        # A simplified regular expression is used to lookahead/lookbehind for common
+        # separator characters to extract the modules used in Requires/Requires.private
+        rewrote_module = line.gsub!(/(?<=[:,\s])(#{deps_pc_modules_pattern})(?=[<=>!,\s])/io, deps_pc_files).present?
+        [line, rewrote_prefix || rewrote_module]
+      end
+      next if modified_lines.none?(&:second)
+
+      pc_file.atomic_write(modified_lines.map(&:first).join)
+    end
+  end
+
   sig { void }
   def rewrite_shebangs
     require "language/node"
diff --git a/Library/Homebrew/test/cleaner_spec.rb b/Library/Homebrew/test/cleaner_spec.rb
index f5f51a29418b0..c6bc63280c3b0 100644
--- a/Library/Homebrew/test/cleaner_spec.rb
+++ b/Library/Homebrew/test/cleaner_spec.rb
@@ -201,6 +201,50 @@
 
       expect(file.read).to eq "brew\n"
     end
+
+    it "modifies Cellar prefix in pkg-config files" do
+      file = f.lib/"pkgconfig/test.pc"
+      file.dirname.mkpath
+      file.write <<~EOS
+        prefix=#{f.prefix}
+        includedir=#{f.include}
+        libdir=#{f.lib}
+        Name: test
+        Description: test module
+        Version: 1.2.3
+        Cflags: -I${includedir}
+      EOS
+
+      cleaner.clean
+
+      expect(file.read).to eq <<~EOS
+        prefix=#{f.opt_prefix}
+        includedir=#{f.opt_include}
+        libdir=#{f.opt_lib}
+        Name: test
+        Description: test module
+        Version: 1.2.3
+        Cflags: -I${includedir}
+      EOS
+    end
+
+    it "does not modify pkg-config files with no rewrites" do
+      file = f.lib/"pkgconfig/test.pc"
+      file.dirname.mkpath
+      file.write <<~EOS
+        prefix=#{f.opt_prefix}
+        includedir=${prefix}/include
+        Name: test
+        Description: test module
+        Version: 1.2.3
+        Cflags: -I${includedir}
+      EOS
+      start_mtime = file.mtime
+
+      cleaner.clean
+
+      expect(file.mtime).to eq start_mtime
+    end
   end
 
   describe "::skip_clean" do