The capacity of crypt stem cells to respond to canonical Wnt signaling enables the adult intestinal epithelium to continuously renew, regenerate after injury and, as a consequence of Apc tumor suppressor mutations, give rise to colon cancers. Likewise, Stat3 signaling is required for stem cell function and therefore also intestinal homeostasis. We previously described that therapeutic inhibition of gp130/Jak/Stat3 signaling suppresses colitis-associated colon cancer in mice [1,2]. We now find that genetic activation of gp130/Jak/Stat3 signaling augments intestinal regeneration and enhances sporadic tumorigenesis in Apc-mutant mice. Conversely, systemic gp130/Jak/Stat3 pathway restriction, or therapeutic Jak inhibition, suppresses regeneration, and also blocks initiation and growth of Apc-mutant mouse tumors, and colon cancer xenografts, without interfering with intestinal homeostasis and despite persisting high Wnt signaling. We identify gp130/Jak/Stat3-dependent induction of Bmi-1 and associated p16/p21 repression as the underlying mechanism. Our findings put in perspective observations that associate complete epithelial Stat3 deletion with reduced crypt stem cell survival and progression of Apc-mutant tumors. We therefore propose that gp130/Jak/Stat3 signaling becomes selectively rate-limiting for Apc-mutant tumor growth by serving as the “rheostat” that links intestinal proliferation to the epithelial wound-healing process hijacked by tumor cells. In turn, our findings provide a rational for therapeutic Jak inhibition in colon cancer.