The 225-issue Nikkei Stock Average decreased 106.63 points, or 0.49 percent, from Tuesday at 21,778.61.
The broader Topix index of all First Section issues on the Tokyo Stock Exchange ended 6.71 points, or 0.42 percent, lower at 1,596.29.
Tokyo shares were under selling pressure as they were affected by Wall Street following the manufacturing purchasing managers' index released Tuesday.
According to the Institute for Supply Management, the index dropped in September to 47.8, the lowest level since June 2009 and below the boom-or-bust threshold of 50 for the second straight month.
By the close of play, machinery, transportation equipment and mining issues comprised those that increased the most.
Increasing issues outnumbered decliners 1,057 to 1,007, while 87 ended unchanged.
The weak manufacturing data and a subsequent rise in the safe-haven yen against the U.S. dollar weighed on a wide range of Japanese manufacturing stocks.
Farm machinery maker Kubota fell 61.5 yen, or 3.7 percent, to 1,590 yen, while Hitachi Construction Machinery decreased 64 yen, or 2.4 percent, to 2,555 yen.
Toyota Motor finished down 87 yen, or 1.2 percent, at 7,159 yen.
On the main section on Wednesday, 1,171.64 million shares changed hands, decreasing from Tuesday's volume of 1,165.64 million shares.