The hypercontractive inequality on the discrete cube plays a crucial role in many fundamental results in the Analysis of Boolean functions, such as the KKL theorem, Friedgut's junta theorem and the invariance principle. In these results the cube is equipped with the uniform measure, but it is desirable, particularly for applications to the theory of sharp thresholds, to also obtain such results for general $p$-biased measures. However, simple examples show that when $p = o(1)$, there is no hypercontractive inequality that is strong enough. In this paper, we establish an effective hypercontractive inequality for general $p$ that applies to `global functions', i.e. functions that are not significantly affected by a restriction of a small set of coordinates. This class of functions appears naturally, e.g. in Bourgain's sharp threshold theorem, which states that such functions exhibit a sharp threshold. We demonstrate the power of our tool by strengthening Bourgain's theorem, thereby making progress on a conjecture of Kahn and Kalai and by establishing a $p$-biased analog of the invariance principle. Our results have significant applications in Extremal Combinatorics. Here we obtain new results on the Turán number of any bounded degree uniform hypergraph obtained as the expansion of a hypergraph of bounded uniformity. These are asymptotically sharp over an essentially optimal regime for both the uniformity and the number of edges and solve a number of open problems in the area. In particular, we give general conditions under which the crosscut parameter asymptotically determines the Turán number, answering a question of Mubayi and Verstraëte. We also apply the Junta Method to refine our asymptotic results and obtain several exact results, including proofs of the Huang--Loh--Sudakov conjecture on cross matchings and the Füredi--Jiang--Seiver conjecture on path expansions.