The structural evolution of tensile-deformed high-density polyethylene (HDPE) at the lamellar level was investigated as a function of strain using a scanning synchrotron small-angle X-ray scattering technique. Intralamellar crystalline block slips were activated at small deformations, whereas stress-induced fragmentation and recrystallization process proceeded at a larger strain, yielding lamellae with polymeric chains preferentially oriented along the stretching direction. The critical strains marking the onset of the destruction of original crystallites and the fibril formation for isothermally crystallized HDPE were at about 0.4 and 1.2, respectively. In the case of a quenched sample, the critical strain was 0.4. In the isothermally crystallized sample two critical values were observed that could be traced back to the existence of two populations of lamellar stacks with significantly different interlamellar amorphous phase thicknesses. This resulted in distinct mobilities of the amorphous domains and, therefore, different moduli or the entangled amorphous networks. Consequently, the strain required to produce the critical network stress, which gave rise to a fragmentation of the crystalline blocks, was different for each stack of crystalline lamellae.