The response of corn (Zea mays L.) and soybean [Glycine max L. (Merr.)] to tillage system and rotation sequence has been investigated for 15 years in Wisconsin. Our objective was to compare yield and economics of conventional and no-tillage systems with different rotation sequences involving 1st-, 2nd-, 3rd-, 4th-, 5th-yr corn or soybean, alternate corn and soybean, and continuous corn or soybean. There was an interaction of corn yield with tillage system and rotation sequence. Averaged over years, tillage increased corn yield 8%, but did not affect soybean yield. Both 1st-yr corn and soybean produced the highest yields at 172 bu acre-1 and 59 bu acre·1 compared to the other six rotation sequences that averaged 148 bu acre-1 and 54 bu acre· 1, respectively Both 1st-yr corn and soybean produced the highest grower return at $80 acre· 1 and $108 acre·1, respectively Interactions for both corn and soybean grower return were found with tillage system and rotation sequence. Averaged over years, tillage increased corn grower return by $2 7 acre-1, but did not affect soybean grower return. It was concluded that 1st –year corn or soybean and alternating corn and soybean were the most profitable rotation sequences over the last 15 years in Wisconsin.