diff --git a/.github/workflows/testmac.yml b/.github/workflows/testmac.yml
index fff05f3ba7a..af600dc249f 100644
--- a/.github/workflows/testmac.yml
+++ b/.github/workflows/testmac.yml
@@ -18,6 +18,14 @@ jobs:
     runs-on: macos-10.15
 
     steps:
+      # The Homebrew Github ships as of 4/12/21 in their Mac 10.15 image uses Bintray for binaries, which is shutting down.
+      # They recommend updating Homebrew to the latest version which pulls binaries from Github Packages instead.
+      # See: https://github.com/Homebrew/discussions/discussions/691#discussioncomment-600559
+      # Remove this step when Github starts shipping a sufficiently new Homebrew
+      - name: Set up Homebrew
+        id: set-up-homebrew
+        uses: Homebrew/actions/setup-homebrew@master
+
       - name: Use cache
         uses: actions/cache@v2
         with:
diff --git a/Makefile b/Makefile
index f3e32f5ab5b..b135cddd054 100644
--- a/Makefile
+++ b/Makefile
@@ -525,7 +525,8 @@ $(LIB_DIR)/libdeflate.a: $(LIBDEFLATE_DIR)/*.h $(LIBDEFLATE_DIR)/lib/*.h $(LIBDE
 	+. ./source_me.sh && cd $(LIBDEFLATE_DIR) && V=1 $(MAKE) $(FILTER) && cp libdeflate.a $(CWD)/$(LIB_DIR) && cp libdeflate.h $(CWD)/$(INC_DIR)
 
 # We build htslib after libdeflate so it can use libdeflate.
-# We make sure to use the htslib that chips inside vcflib.
+# We make sure to use the htslib that ships inside vcflib.
+# We need to do some wizardry to get it to pick up the right build and target system types on modern autotools.
 # We have to do a full build in order to install, to get the pkg-config file so libvgio can link against it.
 # We also have to have the shared libdeflate or we will get complaints that the static one is not position independent.
 # If we need either the library or the pkg-config file (which we didn't used to ship), run the whole build.
@@ -535,7 +536,9 @@ $(LIB_DIR)/libdeflate.a: $(LIBDEFLATE_DIR)/*.h $(LIBDEFLATE_DIR)/lib/*.h $(LIBDE
 # a system path, in case another htslib is installed on the system. Some HTSlib
 # headers look for the current HTSlib with <>.
 $(LIB_DIR)/libhts%a $(LIB_DIR)/pkgconfig/htslib%pc: $(LIB_DIR)/libdeflate.a $(LIB_DIR)/libdeflate.$(SHARED_SUFFIX) $(HTSLIB_DIR)/*.c $(HTSLIB_DIR)/*.h $(HTSLIB_DIR)/htslib/*.h $(HTSLIB_DIR)/cram/*.c $(HTSLIB_DIR)/cram/*.h
-	+. ./source_me.sh && cd $(HTSLIB_DIR) && rm -Rf $(CWD)/$(INC_DIR)/htslib $(CWD)/$(LIB_DIR)/libhts* && autoheader && autoconf && CFLAGS="-I$(CWD)/$(HTSLIB_DIR) -isystem $(CWD)/$(HTSLIB_DIR) -I$(CWD)/$(INC_DIR) $(CFLAGS)" LDFLAGS="-L$(CWD)/$(LIB_DIR) $(LD_UTIL_RPATH_FLAGS)" ./configure --with-libdeflate --disable-s3 --disable-gcs --disable-libcurl --disable-plugins --prefix=$(CWD) $(FILTER) && $(MAKE) clean && $(MAKE) $(FILTER) && $(MAKE) install && ls $(CWD)/$(INC_DIR)/htslib
+	+. ./source_me.sh && cd $(HTSLIB_DIR) && rm -Rf $(CWD)/$(INC_DIR)/htslib $(CWD)/$(LIB_DIR)/libhts* && autoreconf -i && autoheader && autoconf || true
+	+. ./source_me.sh && cd $(HTSLIB_DIR) && (./configure -n 2>&1 || true) | grep "build system type" | rev | cut -f1 -d' ' | rev >systype.txt
+	+. ./source_me.sh && cd $(HTSLIB_DIR) && CFLAGS="-I$(CWD)/$(HTSLIB_DIR) -isystem $(CWD)/$(HTSLIB_DIR) -I$(CWD)/$(INC_DIR) $(CFLAGS)" LDFLAGS="-L$(CWD)/$(LIB_DIR) $(LD_UTIL_RPATH_FLAGS)" ./configure --with-libdeflate --disable-s3 --disable-gcs --disable-libcurl --disable-plugins --prefix=$(CWD) --host=$$(cat systype.txt) $(FILTER) && $(MAKE) clean && $(MAKE) $(FILTER) && $(MAKE) install
 
 # When building vcflib, make sure to force it to use our libdeflate, since we wnt in and configured its htslib to use libdeflate.
 $(LIB_DIR)/libvcflib.a: $(LIB_DIR)/libhts.a $(VCFLIB_DIR)/src/*.cpp $(VCFLIB_DIR)/src/*.hpp $(VCFLIB_DIR)/intervaltree/*.cpp $(VCFLIB_DIR)/intervaltree/*.h $(VCFLIB_DIR)/tabixpp/*.cpp $(VCFLIB_DIR)/tabixpp/*.hpp