C4 photosynthesis involves alterations to leaf development, cell biology and biochemistry. Different lineages of C4 plants use varying mechanisms to generate the C4 pathway. Although the biochemistry of C4 photosynthesis was described around 20 years ago, the phylogenetic distance between Arabidopsis and the traditional C4 models has not facilitated the transfer of knowledge from Arabidopsis research to understanding C4 systems. We show that Cleome, a genus closely related to Arabidopsis, contains species spanning a developmental progression from C3 to C4 photosynthesis. The majority of species we assessed are C3 plants but have increased venation in leaves. Three C3 species have both increased venation and enlarged bundle sheath cells, and there is also a tendency to accumulate proteins and transcripts needed for C4 photosynthesis. Cleome gynandra shows all the characteristics needed for efficient C4 photosynthesis, including alterations to leaf biochemistry, cell biology and development, and belongs to the NAD-dependent malic enzyme subtype. Combined with its phylogenetic proximity to Arabidopsis, the developmental progression from C3 to C4 photosynthesis within the genus provides a potentially excellent new model to increase our understanding of C4 photosynthesis, and provide insights into its evolution.