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For persistent infections of the mammalian host, African trypanosomes limit their population size by quorum sensing of the parasite-excreted stumpy induction factor (SIF), which induces development to the tsetse-infective stumpy stage. We found that besides this cell density-dependent mechanism, there exists a second path to the stumpy stage that is linked to antigenic variation, the main instrument of parasite virulence. The expression of a second variant surface glycoprotein (VSG) leads to transcriptional attenuation of the VSG expression site (ES) and immediate development to tsetse fly infective stumpy parasites. This path is independent of SIF and solely controlled by the transcriptional status of the ES. In pleomorphic trypanosomes varying degrees of ES-attenuation result in phenotypic plasticity. While full ES-attenuation causes irreversible stumpy development, milder attenuation may open a time window for rescuing an unsuccessful antigenic switch, a scenario that so far has not been considered as important for parasite survival., Author summary African trypanosomes escape the mammalian host’s immune system by antigenic variation of their variant surface glycoprotein (VSG) coat. VSGs are expressed from a specialized region in the genome, the expression site (ES), that contains essential expression site associated genes (ESAGs). So far, it was assumed that only successful antigenic switches to an intact expression site are viable. Here we show that unsuccessful VSG switches are not a dead-end, but may rather contribute to the persistence of the trypanosomes at the population level. We have simulated an unsuccessful VSG switch in pleomorphic trypanosomes by expression of a second VSG from a locus without ESAGs. The parasites responded with surprising phenotypic plasticity. All parasites immediately exchanged the surface coat and reduced the abundance of ES-derived transcripts. However, depending on the degree of ES-attenuation, the transgenic trypanosomes either resumed growth, or stopped proliferation. We show that the growth-arrested populations synchronously differentiate to the stumpy life cycle stage and become infective for the tsetse fly. This occurs at low cell densities and in the absence of the quorum sensing factor SIF. Thus, unsuccessful VSG switches are not lethal and cell density-dependent quorum sensing is not the only path to the tsetse fly competence.