The Central Asians just need a point in their remaining two games to book their place at the Qatar competition.
Malaysia sent a young team to Tashkent and the Tigers were second best for much of the match.
The damage was all done in the second half.
2008 AFC Player of the Year Server Djeparov broke the deadlock just after the restart.
Then striker Alexander Geynrikh came off the bench to kill the tie.
The substitute scored after 57 and 65 minutes to give the hosts the three points.
There was still time for Malaysia, preparing for the SEA games, to grab a consolation thanks to Mohamad Zaquan.