Japan striker Shinji Okazaki scored twice with Yasuyuki Konno and Ryoichi Maeda also on target as Alberto Zaccheroni extended his unbeaten run as the country's coach to 18 games with the easy victory on an awful pitch.
Japan lead Group C with 10 points from four matches in the third round of the Asia zone 2014 World Cup qualifying competition and will be one of 10 sides in the fourth round.
"The result was the most important thing today. We want to have already qualified for the final stage before we play our last game against Uzbekistan so the win was crucial," Italian Zaccheroni told reporters before Uzbekistan's match.
That objective was achieved when Timur Kapadze scored the only goal in the 49th minute in Tashkent to send the Uzbeks into the fourth round along with Japan and end North Korea's hopes.
Uzbekistan also have 10 points after their third win from four matches with North Korea, who reached the finals in South Africa last year, third on three points with only two matches remaining.
Having trounced Tajikistan 8-0 in Osaka last month Japan were again expected to steamroller their opponents, ranked 130th by FIFA, but their neat passing game suffered in a difficult first period on the patchy pitch at Dushanbe Central Stadium.
Konno eased the nerves, however, when he converted a rebound in the 36th minute to score his first goal for Japan.
Okazaki headed the second just past the hour mark with substitute Maeda firing home from the edge of the area with eight minutes remaining.
VfB Stuttgart striker Okazaki then wrapped up the scoring in stoppage-time with his 26th goal for the Blue Samurai.
Japan travel to Pyongyang to play North Korea on Tuesday, while Tajikistan, who cannot qualify for the next phase after their fourth defeat in the group, are away to Uzbekistan.
