We study the maximum a posteriori (MAP) decoding of memoryless non-uniform sources over multiple-antenna channels. Our model is general enough to include space-time coding, BLAST architectures, and single-transmit multi-receive antenna systems which employ any type of channel coding. We derive a closed-form expression for the codeword pairwise error probability (PEP) of general multi-antenna codes using moment generating function and Laplace transform arguments. We then consider space-time orthogonal block (STOB) coding and prove that, similar to the maximum likelihood (ML) decoding case, detection of symbols is decoupled in MAP decoding. We also derive the symbol PEP in closed-form for STOB codes. We apply these results in several scenarios. First, we design a binary antipodal signaling scheme which minimizes the system bit error rate (BER) under STOB coding. At a BER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> , this constellation has a channel signal-to-noise ratio (CSNR) gain of 4.7 dB over conventional BPSK signaling for a binary nonuniform source with p <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> Delta <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">=</sub> P(0) = 0.9. We next design space-time linear dispersion (LD) codes which are optimized for the source distribution under the criterion of minimizing the union upper bound on the frame error rate (FER). Two codes are given here: one outperforms V-BLAST by 3.5 dB and Alamouti's code by 12.3 dB at an FER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> for a binary source with p <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> = 0.9, and the other outperforms V-BLAST by 4.2 dB at an FER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> for a uniform source. These codes also outperform the LD codes of constructed under a different criteria. Finally, the problem of bit-to-signal mapping is studied. It is shown that for a binary source with p <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> = 0.9, 64-QAM signaling, and SER = 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> , a gain of 3.7 dB can be achieved using a better-than-Gray mapping. For a system with one transmit and two receive antennas that uses trellis coding with 16-QAM signaling, a 1.8 dB gain over quasi-Gray mapping and ML decoding is observed when MAP decoding is used for binary sources with p <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> = 0.9.