A novel iodine-promoted oxidative cross-coupling/cyclization of 2-(pyridin-2-yl)acetate derivatives and methyl ketones via the cleavage of multiple Csp3-H bonds has been developed, which also achieved efficient cleavage of a C-C bond in the 2-(pyridin-2-yl)acetate derivatives. This protocol represents an elegant molecular fragment assembly of diverse 3-(pyridin-2-yl)indolizines via a formal [3 + 1 + 1] annulation. Notably, the pyridine derivatives serve two pivotal roles to provide two fragments to construct 3-(pyridin-2-yl)indolizine skeletons, rather than the single role in building common indolizines.