The road through Ōtsu-juku is flat and runs along the bank of Lake Biwa, passing the jōkamachi of Zeze Domain.

Before entering Ōtsu-juku, the road made several double-bends intended to slow down any attacker in front of Zeze Castle.

Per the 1843 "東海道宿村大概帳" (Tōkaidō Shukuson Taigaichō) guidebook issued by the Inspector of Highways (道中奉行, Dōchu-būgyō), the town had a population of 14,892 in 350 houses, including two honjin, one waki-honjin, and 71 hatago.

Ōtsu-juku was also the starting point for the Ōsaka Kaidō, an extension of the Tōkaidō which bypassed Kyoto and passed through Fushimi, Hirakata and Moriguchi to central Osaka.

The Hashirii teahouse survived to the early Meiji period, and was later purchased for use as a villa by the nihonga painter Hashimoto Kansetsu in 1915.