A mechanistic study of upconversion from lanthanides is of great importance for the fundamental research of upconversion materials and their diverse frontier applications. However, the most efficient upconversion of lanthanides is still obtained in a commonly used sensitizer-activator coupled system. Here we report a mechanistic investigation on the upconversion of Er3+ through self-sensitization which is applicable for 808, 980 and 1530 nm excitations. It is found that the cooperative energy transfer upconversion followed by cross-relaxation occurring among Er3+ ions plays a critical role in producing and enhancing the red upconversion for the samples with high dopant concentrations (e.g., >20 mol%). The red upconversion color can be further purified and enhanced by mediating the upconversion dynamics through introducing the lanthanides of Ho3+, Tm3+ and Yb3+, which can effectively contribute to the population in the red emitting state. Moreover, the energy migration in the Er-sublattice was also found to be a possible origin for quenching upconversion, which was proved and effectively suppressed by designing a tri-layered nanostructure where the distribution of Er3+ is spatially controllable. Our results gain access into the insight of upconversion dynamics in self-sensitization induced upconversion which would help the search for other new kinds of upconversion materials.